Abstract
To examine the cellular distribution and location of p38alpha/beta isoforms in the lumbar spinal cord of the bone cancer pain rats. Twenty SD female rats weighing 180 - 220 g were randomly divided into 2 groups (n = 10 each): group A (control group): intra-tibial injection of 3 microl Hank's solution; group B (model group): intra-tibial injection of 3 microl MADB-106 mammary gland carcinoma cells of rats (4.8 x 10(3)/microl). Mechanical withdrawal threshold and radiant heat threshold of rats' hind paws were measured every other day from one day before operation until 14 days later. The lumbar 4 ~ 5 spinal cord was removed on the 14th day. The cellular distribution and location of the spinal p38alpha/beta immunoreactivity were detected by immunohistochemistry SABC and double immunofluorescence methods. No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in group A. During the first 6 days of post-operation there was obvious difference in radiant heat stimulus between group A and B (P < 0.05); on the 14th day after operation, mechanical pain threshold and radiant heat threshold in group B were significantly different from that of group A (P < 0.05). The p38alpha/beta immunoreactivity of group B in laminae I approximately IV of dorsal horn showed stronger staining than group A (P < 0.05). Double immunofluorescence confocal micrographs showed that spinal p38alpha and the neuronal marker neuronal N (NeuN) were colocalized in the dorsal horn, indicating that p38alpha was expressed in neurons. Double immunofluorescence micrographs demonstrated that antibodies against p38beta and the microglia marker OX42 labeled the same cell, indicating that p38beta was expressed in microglia. Our studies indicate that p38alpha and p38beta are involved in the generation and maintenance of bone cancer pain states. p38alpha is predominantly expressed in neurons, while p38beta is expressed in microglia.
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